Cis thiophosphoric acid amide esters

ABSTRACT

WHEREIN R1 is alkyl of one to four carbon atoms, R2 is alkyl of one to four carbon atoms, R3 is alkyl of one to five carbon atoms, and X is hydrogen, chlorine or bromine. The compounds are useful pesticides.   The present invention concerns new thiophosphoric acid amide esters of the formula :

Leber et al.

[ Sept. 11, 1973 ClS-Tl-llOPHOSPHORlC ACID AMIDE ESTERS [75] Inventors: Jean-Pierre Leber; Karl Lutz, both of Basle, Switzerland [73] Assignee: Sandoz Ltd., (a/K/A) Sandoz AG,

Basle, Switzerland [22] Filed: July 14, 1970 [21] Appl. No.: 54,837

[30] Foreign Application Priority Data July 18, I969 Switzerland llO28/69 Jan. 21, l970 Switzerland 797/70 [52] US. Cl 260/941, 260/973, 260/984,

[51] Int. Cl A0ln 9/36, C07f 9/l6, C07f 9/72 [58] Field of Search 260/94l [56] References Cited UNITED STATES PATENTS 3,216,894 11/1965 Lorenz et al 260/941 X 3,014,955 12/1961 Beriger 260/941 3,053,729 9/1962 Sun 260/941 X Primary Examiner-Lewis Gotts Assistant ExaminerRichard L. Raymond Attorney-Gerald D. Sharkin, Robert 8'. Honor, Frederick H. Weinfeldt, Richard E. Vila and Walter F.

Jewell [57] ABSTRACT The present invention concerns new thiophosphoric acid amide esters of the formula wherein R is alkyl of one to four carbon atoms, R is alkyl of one to four carbon atoms,

R is alkyl of one to five carbon atoms, and

X is hydrogen, chlorine or bromine.

The compounds are useful pesticides.

16 Claims, No Drawings The present invention relates to new thiophosphoric acid amide esters of formula I,

( 3H: COOR:

possessed by those compounds wherein the -CH, and

-COOR radicals are cis to one another in the crotonic acid radical. Thus, it is to be understood that definitions forthe compounds I essentially contemplate compounds having said cis configuration, although compounds comprising a mixture of the cis form and a certain amount of the trans form are also contemplated. The configuration of compounds I is dependent on the configuration of the starting materials employed in the processes described below, and the process for the production of the starting materials described below result in a predominant proportion of compounds having the cis configuration.

According to the present invention a process for the production of a compound of formula I comprises a. reacting a compound of formula V,

wherein R R and X are as defined aboveg and Y is halogen,

with an amine of formula IV,

RQNH,

Z is hydrogen or an alkali metal, in the presence of an acid acceptor when Z is hydrogen, and optionally in the presence of an acid acceptor when Z is an alkali metal.

Preferably Y is chlorine or bromine, and Z is hydrogen or sodium.

In one method of effecting process a) of the invention, a compound of formula [V and an acid acceptor such as triethylamine, trimethylamine, dimethyl aniline, diethyl aniline or sodium carbonate, are added at a temperature of between 20 and +50C, preferably between l0 and 0C, to a compound of formula V in an inert solvent, e.g., an aromatic hydrocarbon such as toluene or xylene, a halogenated hydrocarbon such as chlorobenzene or chloroform, or an ether such as dioxane, over a period of between one-half hour and 2 hours.

Preferably an equivalent amount of the compound of formula IV with respect to the compound of formula V is employed, and the amount of the acid acceptor is preferably such as to be equivalent with respect to the compound of formula V, for taking up the hydrohalic acid produced in the reaction. However, it will be appreciated that when a compound of formula IV itself is employed as acid acceptor, then the amount of the compound of formula IV is preferably two equivalents with respect to the compound of formula V.

The reaction mixture is stirred at room temperature over a'period of between [0 and 20 hours. The solvent is subsequentlyremoved in a vacuum at a bath temperature of between 20 and 50C. The residue is distilled in a high vacuum. The pure compound of formula I is obtained as a colourless oil which can be distilled without decomposition. I

In one method of effecting process b) of the invention, a compound of formula III and an acid acceptor such as triethylamine, trimethylamine, dimethyl aniline or diethyl aniline, are added at a temperature of between -20 and +50C, preferably between 0 and 20C, to a compound of formula VI in an inert solvent,

e.g., an aromatic,hydrocarbon such as toluene or xylene, a halogenated hydrocarbon such as chlorobenm wherein R is as defined above, and

-zene or-chloroform, or an ether such asdioxane, over a period of between one-half hour and 2 hours.

Preferably an equivalent amou'ntof the compound of formula II] with respect to the'compou'nd' of formula VI is'employed, and the amount of acid acceptor is preferably such as to be equivalent with respect to the compound of formula-Vl,"forthe acceptance of displaced Yradicals. t t The reaction mixture is subsequently stirred at 20C over a period of between 20 and hours,and the reaction mixture is then worked up in the usualmanner, to yield the compound-of formula I. r The compound of formula V employed as starting material in process a) above may be produced by reacting a compound of formula ll,

wherein R,, X and Y are as defined above,

with a compound of formula III, optionally in the pres ence of an acid acceptor.

The resulting reaction mixture may be employed directly for reaction with the compound of formula IV in accordance with process a) above without isolation of the compound of formula V. One method of effecting process a) of the invention starting with the production of a compound of formula V and continuing through to the production of a compound of formula I, without isolation of the compound of formula V, comprises adding preferably at least one equivalent of a compound of formula III, at a temperature of between -20 and +50C, preferably between -lC and room temperature, to a compound of formula II in an inert solvent, e.g., an aromatic hydrocarbon such as toluene or xylene, a halogenated hydrocarbon such as chlorobenzene or chloroform, or an ether such as dioxane, over a period of between one-half hour and 2 hours, in the presence of an acid acceptor such as triethylamine, trimethylamine, dimethyl aniline or diethyl aniline.

Preferably the acid acceptor is present in an amount such as to be equivalent with respect to the compound of formula II, for the acceptance of displayed Y radicals.

Without isolation of the compound of formula V,

- produced by the preceding process, from the reaction mixture, a mixture of an amine of formula IV, preferably in an equivalent amount, with an acid acceptor, such as triethylamine, trimethylamine, dimethyl aniline or diethyl aniline, preferably tri-n-butyl amine, preferably also in an equivalent amount, is added at a temperature of between and +50C, preferably between l0C and room temperature, over a period of between one-half hour and 2 hours to the reaction mixture. The reaction mixture is stirred at room temperature for about 20 hours. The reaction mixture is then worked up in the usual manner to yield the compound of formula I.

In an alternative method of effecting process a) of the invention commencing first with the production of a compound of formula V and then continuing through to the production of a compound of formula 1, without isolation of .the compound of formula V from the reaction mixture, a compound of formula II is reacted with a compound of formula III in a manner such as hereinbefore described, but in the absence of an acid acceptor. Subsequent reaction of the resulting compound still contained in the reaction mixture with a compound of formula IV may be effected by employing at least three equivalents of the compound of formula IV, which compound in addition to reacting with the compound of formula V, also serves as acid acceptor, by reacting with the hydrohalic acid produced during the overall reaction, including the reaction between the compounds of formulae II and Ill.

The production of a compound of formula VI, employed as starting material in process b) above for the production of a compound of formula I, may be effected by reacting a compound of formula II with a compound of formual IV, preferably in equivalent amounts, in the presence of an acid acceptor.

As already indicated, the compounds I of the invention essentially contemplate compounds wherein the -CH and -COOR radicals are cis to one another in the crotonic acid radical. This configuration, or a predominant proportion of compounds of formula I having this configuration (more than 80 by weight) can be achieved by preparing the above compounds of formula II in a specific manner. In general, the compounds of formula Il may be produced by reacting a phosphoric oxxyor thiochloride or bromide with a compound of formula VI],

CI-I COCHXCOOR Vll wherein R and X are as defined above, or with a salt thereof, in the presence of an acid acceptor. The compounds of formula II predominantly have a cis configuration in the crotonic acid radical (i.e. the -CH group is cis to the -COOR group) when an organic base, e.g., tri-n-butylamine or triethylamine, is used as acid acceptor. When, for example, sodium bicarbonate is used as acid acceptor, the portion of cis configuration in the crotonic acid radical of the compound of formula II is smaller than when triethylamine is used. When, for example, a sodium acetoacetic acid ester is used in place of the acetoacetic ester of formula VII and'an acid acceptor, then compounds of formula Il=predominantly having the trans form in the crotonic acid radical are obtained. Thus, in order to obtain compounds of the desired high proportion of cis configuration,- the acid acceptor employed in the production of compounds II needs to be, for example, tri-n-butylamine or triethylamine, and the sodium acetoacetic acid ester is normally not a suitable starting material in the production of compounds II.

In the case wherein a compound of formula II is required as a starting material in a process for the eventual production of a compound I according to process a) above, and involving the intermediate production of a compound of formula V, the process may be effected by reacting a compound of formula VII with a phosphorus thiohalide, e.g., phosphorus thiochloride, in the presence of an acid acceptor, e.g., tri-n-butyl amine, and without isolating the resulting compoundof formula II from the reaction mixture adding thereto a compound of formula III together with an acid acceptor. After the reaction, without isolating the resulting compound of formula V, a compound of formula IV together with an acid acceptor are added to the reaction mixture under the conditions as hereinbefore described, and the reaction allowed to proceed. The resulting reaction mixture is worked up in conventional manner to yield the compound of formula I.

Thethiophosphoric acid amine esters of fonnula I obtained in accordance with the invention areoils which can be distilled in a high vacuum without decomposition. When they are produced in accordance with the processes a) and b) described above, the same ratio of the cis with respect to the trans isomer thereof in the crotonic acid radical is obtained as is present in the starting materials of formulae V and VI and'hence II respectively. The compound I are soluble in organic solvents and may be readily emulsified with water.

The compounds of formula I are .useful pesticides. More particularly, the compounds possess insecticidal, acaricidal and nematocidal properties. They are effective against chewing and sucking insects, particularly against spider mites.

The compounds have a low level of toxicity in warm- 1 tection of plants and animals againstnoxious organisms, e.g., insects, mites and nematodes.

The combatting of noxious organisms may be carried out by conventional methods, e.g. by treating the subjects or locus to be protected with a composition containing a compound of formula I as active agent. For use as pesticides, e.g. in plant protection, the compounds of formula I may be added to carrier materials to form dusting or spraying agents, e.g., solutions or dispersions, employing water or suitable organic solvents, e.g., alcohol, petroleum or tar distillates, optionally in combination with emulsifying agents, e.g., liquid polyglycol ethers derived from high molecular weight alcohols, mercaptans or alkyl phenols with an alkylene oxide. Suitable organic solvents such as ketones, aromatic, optionally halogenated hydrocarbons, or mineral oils, may also be added as solution aids.

Spraying and dusting agents may contain the usual inert carrier materials, e.g., talc, diatomaceous earth, bentonite, pumice, or other additives such as cellulose derivatives and the like, as well as conventional wetting agents and adhesives.

The compounds of formula I may be present in compositions as mixtures with other known active materials. The compositions may contain between 2 and 90 preferably between 5 and 50 by weight of active agent. For application, the compositions, which may be in diluted form, may contain between 0.02 and 90 preferably between 0.1 and 20 by weight of the compound of formula I.

It should be understood that it is not essential that the com-pounds of formula I be free from the trans isomer thereof for use in pesticidal compositionsThis is pertinent in the case wherein in theprocess of production of the compounds of formula I, a certain amount of trans isomer thereof is also produced." 7

The following examples are illustrative of concentrates containing a compound of formula I as active pesticidal agent.

a. 25 parts by weight of a compound of formula I are mixed with 25 parts by weight of isooetylphenyldecaglycol ether and 50 parts by weight of xylene, whereby a clear solution is obtained, which can easily be emulsified in water. The concentrate is diluted with water to the desired concentration before use. i

b. 25 parts by weight of a compound of formula I are mixed with 30 parts by weightof isooctyl phenylocataglycol ether and 45 parts by weight of a-petroleum fraetionhavinga B.P. of 2l0280 (0 0.92). The concentrate is diluted withwater to the desired concentration before use.

mixed with parts by weightof isooctylphenyloctaglycol ether. A clear concentrate is obtained, which may be readily emulsified in water and which is diluted with water-to the desired concentration before use. The following application examples illustrate'the effectiveness of the compounds of formula I. Insecticidal effect against Bruchidius obtectus (bean weevil) contact effect 0.1 to 0.2 cc of en emulsion containing 0.0125 of the active agent of formula l are sprayed with a spraying nozzle into a number of 7 cm diameter Petri dishes. The emulsion in the dishes is then dried for about 4 hours, and then Bruchidius images are placed in each 50 parts by weight of a compound of formula I are I dish which is covered with a lid of fine mesh brass wire grating. The animals are kept without food at room temperature.

After 48 hours the rate of mortality is determined. The mortality rate is indicated as a precentage. means that all the bean weevils were killed, 0 means that no bean weevil was killed. The evaluation is given in the following Table l.

insecticidal effect against Ephestia Kiiehniel la (flour moth) contact effect Petri dishes having a diameter of 7 cm, each containing 10 caterpillars of 10 to 12 mm length, are sprayed by means of a spraying nozzle with 0.1 to 0.2 cc of an emulsion containing 0.05 of the active agent of for- TABLE :2 (unlmuml "lAliLl'I 'l llulu of mm'lnllty Rule of umlln lly In pi-rm'nlv nllm' In [it'llllll Actlvo agent days Acllvo ugmll :iflvr ll-l hours (1,1150 s 100 (11130 s im.

7' {I l. 1) 11-031mm 0- 1=o1tcooc1n ll-CglizNII 0-( 3=cn-c00c1n cm cm GU30 S 100 01130 s 100 y P P i-C3H1NII 0C=CH-c00CIn CzH NII O-C=CHCOOi-C:II.-

i CH3 CH3 C2H5O S 100 g I u-CgHyNH OC=CHCOOCH: Insecticidal effect against Carausius morosus E (Indian rod locust) feed effect C H O s 100 2 Tradescantia branches are immersed for 3 seconds in- 2 0 5 an emulsion containing 0.0125 of a compound of formula 1. After drying, each of the Tradescantia CtHsNH I Oi-CaH1 branches is inserted into a small glass tube filled with water, and this is placed in a glass dish. 10 Carausius larvae in the second stage of development are counted into each dish which is then closed with a wire mesh lid.

After 5 days the rate of mortality is determined by counting out the live and dead animals. The mortality rate is indicated as a percentage. 100 means that all the rod locusts were killed, 0 means that no rod locust was killed. The evaluation is indicated in the following Table 3.

i raisin a Rate of mortality in percent- Active agent after 5 days CHaO S 100 n-CsHrNH O?=CH-COOCH3 CHaO S 100 P i-CaIl'7NII O(]}=GH-COOCH:

(JzlIaU s .1uo

Il-C3ll7Nll O(IJ =:CIIUOOGH:|

(Ella OIIJO S 100 P CzHsNH O(]7=CHCO0l-CJH:

ins cticidal ctlect against Aphis fabae (black bean aphid) contact efiect Broad bean plants (Vicia faba) are sprayed to run off with a spraying liquor containing 0.0125 of active agent. The broad bean plants are strongly infected with all the forms of development of the black bean aphid (Aphis fabae).

After 2 days the rate of mortality is determined. The mortality rate is indicated as a percentage. 100 means that all the bean aphids were killed, 0 means that no bean aphid was killed. The evaluation is indicated in the following Table 4.

Nematocidal effect against Panagrellus redivivus (paste nematode) 1 cc of an aqueous suspension of Panagrellus redivivus, containing about 120 nematodes, is placed in a small cup having a diameter of 5.5 cm and a height of 3.2 cm, and containing 7 g of Terralite. 1 cc of an emulsion containing a compound of formula I is then spread over the Terralite. After 48 hours the contents of the cup are examined in accordance with Baermann's extraction method (G.Baermann, Meded.Geneesk.Lab.'- Weltefreden 1917, 41-47), and the live nematodes are counted out under a binocular magnifying glass. The rate of mortality is indicated as a range of 0 to 9 (9 maximum effect, no live nematodes, 0 no effeccover live nematodes). The evaluation is indicated in the following Table 5.

The following Examples illustrate the prmimnkm of the compounds, but in no way limit the wipe of 0m in vention. The temperatures'are indicated in degiees Centigrade.

EXAMPLE 1: 0-( l Carboisopropoxy-l -propen-2-yl O-methyl-N-ethyl-phosphorothioamidate (process a OC=CHCOOCH(Cllz)g CHaO pyl ester and 178 g (1.05 mols) of'thiophosphoryl chloride while stirring and cooling to about 3 during the course of 1 hour. The solution which turns viscous is stirred at to 3 for a further half hour, whereby the solution is mixed as thoroughly as possible. As soon as a viscous oil starts to separate, 20 cc of toluene are added. 1.2 liters of petroleum ether are added, the mix-' ture is stirred for a short period and the tributyl ammonium chloride is filtered off. The filtrate is concentrated in a vacuum at a bath temperature of 30. 128 g (4.0 mols) of methanol are added to the residue as rapidly as possible at 0 and the mixture is stirred at 0 for 4 hours. 226 g of a 70 aqueous solution of ethylamine (3.5 mols) are then added at within one-half hour, and the mixture is stirred at 0 for a further onehalf hour. The reaction mixture is extracted twice in a separatory funnel with 120 cc amounts of approximately hydrochloric acid (25 cc of concentrated hydrochloric acid with 100 g of crushed ice). The separation of the phases during the first washing with aqueous hydrochloric acid is effected without the addition of petroleum ether; petroleum ether is preferably added during the second washing with aqueous hydrochloric acid in order to complete the separation. The petroleum ether phase isagain washed with water and with hydrogen carbonate solution, is dried with sodium sulphate, and the solventis removed. The resulting 0- 1 carboisopropoxyl propen-2-yl)-0-methyl-N-ethylphosphorothioamidate hasa B.'P. of 8789/5.10" mm of Hg. n 1.495.

Analysis: C H NO PS Molecular weight: 281.3 Calculated: C 42.7 H 7.2 N 5.0 P 11.0 S 11.4

Found: 42.1 6.8 5.3 11.0 10.9 1 1 EXAMPLE 2: 0-(1Carboisopropoxy-l-propen-2-yl)- O-ethyl-N-npropyl-phosphorothioamidate (process a) 286.7 g (1 mol) of cis-0*ethy1-0-(l-carboisopropoxy- 1-propen 2-yl)-thionophosphorochloridate [Cl(C,1-l,,. O)P(S)OC(CH )=CHCOOCH(CH dissolved in 1 liter of toluene, are'added to a mixture of.59.1 g .(1 mol) of propylamine and 101.2 g (1 mol) of triethylamine at a reaction temperature of 20 with '2 hours. The reaction mixture is stirred at 20 for'a further 36 hours, and the precipitated triethylamine hydrochloride is subsequently filtered off. The filtrate is washed with water, dried, the solvent is removed by evaporation, and the resulting product is distilled in a vacuum. 0-( l-Carboisopropoxy- 1 propen-2-yl)-0-ethyl-N-npropylphosphorothioamidate has a 8.1. of 87-89 at a pressure of 5.10' mm of Hg. It is obtained almost exclusively with the cis form in the crotonic acid radical. "D20 Analysis: C,,H NO,PS Molecular weight: 309.4 Calculated: C 46.6 H 7.8 N 4.5 P 10.0 S 10.4

% Found: 46.7 7.8 4.8 9.9 10.6

The 0-ethyl-0-(1carboisopropoxy-1-propen-2-yl)- thioph sphorochloridate, required as starting material, may be produced as follows:

277.1 g (1 mol) of cis-0-( l-carboisopropoxy-lpropen-Z-yl)rthiophosphorodichloridate are added at a reaction temperature of 5 to 276 g (6, mols) of ethanol. The temperature is then allowed to rise to 1012, and the mixture is kept at this temperature for one-half hour. The reaction mixture is subsequently diluted with 500 cc of toluene and is made neutral with 200 cc of a 20 caustic soda solution at 10 to 5 while stirring vigorously. The reaction mixture is added to 200 cc of ice water, the organic phase is separated, is washed well with a sodium hydrogen carbonate solution and subsequently with water, is dried with magnesium sulphate, filtered and concentrated by evaporation in a vacuum at 40. The resulting product may be purified by distillation in a high vacuum. It is also possible to use the crude product in the reaction for the production of the corresponding compound of formula I.

0-( 1 -Carboisopropoxy-1-propen-2-y1)-thiophosphoro-dichloridate is obtained in the following manner:

105 g (1.03 mols) of triethylamine are added at 10 while stirring within one-half hour to a mixture of 169.4 g (1 mol) of thiophosphoryl chloride, and 144.2 g (l mol)-of acetoacetic acid isopropyl ester, whereby triethylamine hydrochloride precipitates. The reaction mixture is subsequently stirred at a temperature'between 10 and +10 for one-half hour, and at for 320 g lmol). of 0-( 1 chlorof 1 carbethoxy-l -pr open- 2-yl)-N-n propyl-phosphoramidochloridothionate [Cltrans 9:1) are dissolved inamixture of 500 cc of tolufe'ne and 500cc of chloroform. A mixture of 32.1 g (1 ,mol) of methanol and1'101.2 g (1 mol) of triethylamine is added at 0 to this solution within Z-hours. Thereaction mixture is then stirred at 0 for 5 hours','and subsequently at 20 for 100 hours. The precipitated triethylamine hydrochloride is filtered off. and the filtrate is washed, driedand distilled. The resulting 0-( l-chlorolcarbethoxy-l propen-Z-yl )-0-methyl-Nn-propyl-phosphorothioamidate has a 8.1. of 107 at 0.01 mm of Hg. The ratio of the cisztrans isomers in the crotonic acid radical amounts to 9:1.

Analysis: C H,,ClNO,PS Molecularweight: 315.8

Calculated: C 38.0 H 6.1 C1 11.2 N 4.4 P 9.8 185 10.2 v Found: 38.4 6.3 11.5 4.4 9.7 10.8

The 0-( l-chloro-lcarbethoxy-1-propen-2-yl)-N-npropyl-phosphoroamidochloridothionate, required as starting material, may be produced in the following manner: a

A solution of 297.5 g (1 mol) of '0-(l-chloro-1- carbethoxyl propen-2-yl )-thiophosphorodichloridate in 1 liter of toluene is reacted at with a mixture of 59.1 g (1 mol) n-propylamine ri-orpoylamine and 102 g (1 mol) of triethylamine during the course of 1 hour. The reaction mixture is subsequently stirred at 0 for one-half hour, and at 20 for 1 hour. The precipitated triethylamine hydrochloride is subsequently filtered off, the filtrate 1s washed with water, dried with sod1um l h t d d nll wherein X signifies a hydrogen atom, which are ob- 0-( l -Chlorol -carbethoxy-l-propen-2-yl)-th1ophostamed as a mixture with the trans isomer in some cases, phorodichloridate may be obtained in a manner analothe ratio of the cisztrans isomers 1n the crotomc acid gous to the d chlor date descr bed n Example 2, radical being substantially the same as thatof the start- The following compounds (see Table WhlCh follows) mg materials, may be obtained ina manner analogous of formula I, to that described 1n Examples 1, 2 and 3.

Ratio Analysis, percent cisztrans Molec in the cm- Calculated Found Empirical ular 13.13.. tonic acid R5 formula weight C. 1in'- radical C II N l S C II N l S CH5 C7HHNO4PS 230.2 11-80 1.501 Cis 35.1 5.0 5.0 12.0 13.4 85.0 0.2 0.0 13.0 13.4 CH: 0111051011 8 201.3 80-01 1.501 018 40.4 0.8 5.2 11.0 12.0 40.3 0.1 5.1 11.0 12.0 CH: CDHIBNO4PS 201.3 10-80 1.408 018 40.4 0.8 5.2 11.0 12.0 41.0 0.3 5.5 12.1 13.0 105H: C11H22NO4PS 205.3 84-85 1.401 0:1 44.1 1.5 4.1 10.5 10.0 44.4 1.5 5.1 10.8 11.1 CH: 01011100104188 281.3 88-80 1.401 85:15 42.1 1.2 5.0 11.0 11.4 42.1 1.3 5.1 10.0 11.1 CH: 01110510188 253.3 84 1.504 05:5 31.0 0.4 5.5 12.2 12.1 31.1 0.5 5.0 12312.0 H3 C1H11NO4PS 253.3 88 1.503 03:1 31.0 0.4 5.5 12.2 12.1 38.3 0.4 5.5 12.0 12.0 CH: ommNoms 201.3 -00 1.400 05:5 40.4 0.8 5.2 11.0 12.0 40.3 0.8 5.2 11.0 12.3 CH: omm Noms 281.3 18 1.400 Cis 42.1 1.2 5.0 11.0 11.4 42.4 1.2 5.2 11.3 11.4 0111 (31110010118 201.3 01-02 1.500 00:10 40.4 0.8 5.2 11.0 12.0 40.3 0.0 5.0 11.4 12.4 CH: 010112001011 8 281.3 02-04 1.400 :15 42.1 1.2 5.0 11.0 11.4 43.0 1.0 5.1 11.5 12.0 CH; C11H23NO4PS 205.3 04-00 1.405 00:10 44.1 1.5 4.1 10.5 10.0 45.5 0.0 4.5 11.1 11.0 011: 011110100 23 205.3 81 -80 1.403 05:5 44.1 1.5 4.1 10.5 10.0 44.5 1.4 4.8 10.1 11 CH: CHHHNOJPS 300.4 00-08 1.403 00:10 40.0 1.8 4.5 10.0 10.4 40.1 1.0 4.1 10.8 10 CH0 00111431011 8 201.3 81 1.400 018 40.4 0.8 5.2 11.0 12.0 30.1 0.1 5.5 11.1 12.3 CH5 ommuNmPs 281.3 85-80 1.405 00:10 42.1 1.2 5.0 11.0 11.4 41.1 1.1 5.4 11.1 11.0 CH3 Ci1Hz2NO4PS 205.3 80 1.403 01:3 44.1 1.5 4.1 10.5 10.0 44.4 1.1 4.1 10.0 10.0 CH; CuHgzNOdS 205.3 81-84 1.480 Cis 44.1 1.5 4.1 10.5 10.0 44.1 1.5 4.4 11.2 11.1 CH: C0H0No1Ps 205.3 03-04 1.403 05:5 44.1 1.5 4.1 10.5 10.0 45.0 1.0 5.0 10.0 11.0 CH1 C13Hz5N01PS 323.4 01-03 1.400 85:15 48.3 8.1 4.3 0.0 0.0 41.1 8.1 4.2 10.1 10.8 01H: C:H::N0iPs 253.3 81-88 1.504 05:5 31.0 0.4 5.5 12.2 12.1 38.5 0.4 5.8 11.8 13.1 02H: 0:11: 510418 201.3 81 1.400 015 40.4 0.8 5.2 11.0 12.0 40.0 1.0 0.1 11.0 11.3 02115 C4H11NO4PS 201.3 84-80 1.408 (315 40.4 0.8 5.2 11.0 12.0 40.4 0.1 4.0 12.5 12.3 0213, C H NO PS 281.31 8581 1.400 05:5 42.1 1.2 5.0 11.0 11.4 42.0 1.3 5.1 11.0 11.5 01115 01 111531011 8 205.3 05-00 1.403 05:5 44.1 1.5 4.1 10.5 10.0 45.2 1.5 4.0 10.1 11.3 04H: 00112251011 8 205.3 80-00 1.402 05:5 44.1 1.5 4.1 10510. 44.5 1.5 4.0 10.8 11.3 (32H, C H NOdS 281.3 0008 1.400 05:5 42.1 1.2 5.0 11.0 11.4 42.1 1.1 5.3 10.1 12.0 0211: 001122010198 205.3 05-00 1.401 01:3 44.1 1.5 4.1 10.5 10.0 45.0 1.0 4.0 11.2 11.3 01H: O12H:1NO:PS 300.4 02-04 1.402 Ois 40.0 1.8 4.5 10.0 10.4 40.1 8.0 4. 10.5 10.2 04H: C12Hz4NO4PS 300.4 88-80 1.480 05:5 40.0 1.8 4.5 10.0 10.4 40.8 1.0 4.3 10.3 10.4 C4H5 C10Hz NO4PS 281.3 03-04 1.402 Cis 42.1 1.2 5.0 11.0 11.4 42.3 1.3 5.2 11.0 11.4 01H: C11H22N04PS 205.3 80-02 1.480 05:5 44.1 1.5 4.1 10.5 10.0 44.0 1.3 4.0 10.0 11.1 o 0:13 C1:H:1N0iPs 300.4 04 1.480 Cis 40.0 1.8 4.5 10.0 10.4 40.4 8.0 4.0 10.8 10.8 .10511: 10:11: 01H: C12H24NO|PS 300.4 01-02 1.485 Cis 40.0 1.8 4.5 10.0 10.4 40.1 1.0 4.1 10.2 10.4 -11C4H9 101B: 0,121 CHIIIBNOlPS 331.4 03-04 1.480 Cis 40.8 8.4 4.2 0.2 0.5 40.1 8.5 4.2 0.4 0.2 1C4H0 11C1H0 C2H5 C11H28NO4PS 337.4 104-06 1.484 018 49.8 8.4 4.2 9.2 9.5 49.4 8.7 4.4 9.9 9.6 OH: CH; 00:11: 0111011011 8 201.3 02 1.502 80:11 40.4 0.8 5.2 11.0 12.0 40.5 0.8 5.1 12.1 13.4 CH3 CzHu 1161111 C10H111NO4PS 281.3 96 1.498 9525 42.7 7.2 5.0 11.0 11.4 42.8 7.3 5.6 11.6 12.2 CH3 iC1H1 11031-11 CuHzzNOflS 295.3 92 1.494 :10 44.7 7.5 4.7 10.5 10.9 45.1 7.8 5.0 10.7 11.4 0:113 CH; 1103H1 010114011011 8 281.3 02-04 1.405 05:5 42.1 1.2 5.0 11.0 11.4 43.0 1.2 5.0 11.4 11.0 04H: nCaH-l 00:11: 00111101011 8 300.4 101-05 1.401 81:13 40.0 1.8 4.5 10.0 10.4 40.3 1.8 4.8 0.0 10.2 01H: 1C:H1 1101111 01111001011 81 300.4 08 1.488 00:10 40.0 1.8 4.5 10.0 10.4 41.0 1.1 5.0 10.2 11.0 110111: 0411: 110111: 01411115101881 300.4 104-05 1.400 05:5 40.0 1.8 4.5 10.0 10.4 41.0 1.0 4.2 10.5 10.8 .00111: nCaH1 nCaH: CHHNNOAPS 323.4 111 1.480 05:0 48.3 8.1 4.3 0.0 0.0 48.4 8.0 4.0 0.1 10.0 .ncm: 1C:H1 1103111 ou'mgNoms 323.4 102-03 1.481 00:10 48.3 8.1 4.3 0.0 0.0 48.0 8.3 3.1 0.1 10.4 004111 CHHMNmPS 205.3 011-01 1.400 Cis 44.1 1.5 4.1 10.5 10.0 45.0 1.0 5.1 10.8 11.2 004111 011110110403 300.4 115-011 1.488 ()is 40.0 1.8 4.5 10.0 10.4 40.3 1.8 4.1 10.3 10.3 1104111 011111101011 0 323.4 104-05 1.480 015 48.3 8.1 4.3 0.0 0.0 41.0 8.0 4.0 0.8 10.2 1101111 01111411101811 323.4 04-00 1.483 Cls 48.3 8.1 4.3 0.0 0.0 48.0 8.1 3.0 0.0 0.0 10:11: C0H0N0u s 201.3 01 1.400 03:1 40.4 0.8 5.2 11.0 12.0 40.4 0.1 4.8 11.0 12.0 10:11: 0011011041 8 205.3 05-01 1.405 05:5 44.1 1.5 4.1 10.5 10.0 44.4 1.4 4.8 10.8 12.0 10:11: C11Hz-1NO1PS 205.3 80 1.402 85:15 44.1 1.5 4.1 10.5 10.0 45.4 8.0 4.0 10.3 10.8 103111 C10 :5N01Ps 281.3 01-03 1.402 01:3 42.1 1.2 5.0 11.0 11.4 43.3 1.3 5.0 10.1 11.0 10 111 G12H2|NO4PS 300.4 00-02 1.480 05:5 40.0 1.8 4.5 10.0 10.4 40.5 1.1 4.0 10.0 10.3 1C:H1 C11H25NO1PS 323.4 1.488 00:10 48.3 8.1 4.3 0.0 0.0 48.1 1.0 4.3 0.0 0.8 10311: 011115111011 8 205.3 05-01 1.400 01:3 44.1 1.5 4.1 10.5 10.0 45.2 1.0 4.1 10.8 11.0 103111 (31: :moms 3004 08-00 1.488 03:1 40.0 1.8 4.5 10.0 10.4 41.3 1.8 4.1 10.2 10.8 103111 CHHZBNOlPS 323.4 101-03 1.481 01:3 48.3 8.1 4.3 0.0 0.0 48.3 8.1 4.5 0.0 0.2 103111 013114010011 8 323.4 01-08 1.485 01:3 48.3 8.1 4.3 0.0 0.0 48.4 8.1 4.3 0.0 10.1 103E: CHHQQNOJS 331.4 100-03 1.483 015 40.8 8.4 4.2 0.2 0.5 50.2. 8.5 4.1 0.4 0.1 10:11: Ci1H22NO1PS 205.3 00-02 1.488 015 44.1 1.5 4.1 10.5 10.0 44.1 1.3 4.0 10.8 11.0 10:11: Oi2H24NO1PS 300.4 011-112 1.485 Cis 40.0 1.8 4.5 10.0 10.4 40.4 1.1 4.5 10.3 10.4 10311: Ci1H2aNO1PS 323.4 011-101 1.485 Cis 48.3 8.1 4.3 0.0 0.0 41.0 1.0 4.8 10.0 10.0 10311: C1:H::N0i1 s 323.4 80 1.482 015 48.3 8.1 4.3 0.0 0.0 41.0 8.0 3.0 10.2 0.0 0:115 C10HQQNO4PS 281.3 01-00 1.400 88:12 42.1 1.2 5.0 11.0 11.4 42.1 1.1 4.0 11.1 11.0 02111 cmu NoiPs 281.3 81-00 1.401 88:12 42.1 1.2 5.0 11.0 11.4 42.1 1.4 4.0 10.0 12.1 10. 011: 11C3H1 11C:H: 011114401011 8 205.3 102 1.400 00:10 44.1 1.5 4.1 10.5 10.0 45.4 1.4 4.0 11.1 12.3 @2115 0,11 11C3H: 01111121001188 205.3 00 1.403 00:10 44.1 1.5 4.1 10.5 10.0 44.3 1.2 4.8 10.3 10.0 g c 0H 03H: 0111121110188 205.3 104-00 1.403 05:5 44.1 1.5 4.1 10.5 10. 44.0 1.3 4.5 10.2 10.8

What is claimed is: 1. A compound of the formula:

wherein R, is alkyl of one to four carbon atoms, R, is alkyl of one to four carbon atoms, R is alkyl of one to five carbon atoms, and X is hydrogen, chlorine or bromine, in which -CH is cis to the -COOR in the crotonic acid moiety.

2. The compound of claim 1, wherein R, is methyl, R is methyl, R is isopropyl and X is hydrogen.

3. The compound of claim 1, wherein R, is methyl, R is ethyl, R is methyl and X is hydrogen.

4. The compound of claim 1, wherein R, is methyl, R and R are ethyl and X is hydrogen.

5. The compound of claim 1, wherein R, is methyl, R is ethyl, R, is isopropyl and X is hydrogen.

6. The compound of claim 1, wherein R, is methyl, R is n-propyl, R is methyl and X is hydrogen.

7. The compound of claim 1, wherein R, is methyl, R is n-propyl, R is ethyl and X is hydrogen.

8. The compound of claim 1, wherein R, is methyl, R, is isopropyl, R is methyl and X is hydrogen.

9. The compound of claim 1, wherein R, is methyl, R and R are isopropyl and X is hydrogen.

10. The compound of claim 1, wherein R, is ethyl, R, is methyl, R is ethyl and X is hydrogen.

11. The compound of claim 1, wherein R, is ethyl, R is isopropyl, R is methyl and X is hydrogen.

12. The compound of claim 1, wherein R, is ethyl, R and R are isopropyl and X is hydrogen.

13. The compound of claim 1, wherein R, is n-propyl, R is methyl, R is isopropyl and X is hydrogen.

14. The compound of claim 1, wherein R, is isopropyl, R, is methyl, R is ethyl and X is hydrogen.

15. The compound of claim 1, wherein R, is methyl,

R, is n-propyl, R is ethyl and X is chlorine.

16. A compound of claim 1 in which R; is isopropyl and X is hydrogen. 

2. The compound of claim 1, wherein R1 is methyl, R2 is methyl, R3 is isopropyl and X is hydrogen.
 3. The compound of claim 1, wherein R1 is methyl, R2 is ethyl, R3 is methyl and X is hydrogen.
 4. The compound of claim 1, wherein R1 is methyl, R2 and R3 are ethyl and X is hydrogen.
 5. The compound of claim 1, wherein R1 is methyl, R2 is ethyl, R3 is isopropyl and X is hydrogen.
 6. The compound of claim 1, wherein R1 is methyl, R2 is n-propyl, R3 is methyl and X is hydrogen.
 7. The compound of claim 1, wherein R1 is methyl, R2 is n-propyl, R3 is ethyl and X is hydrogen.
 8. The compound of claim 1, wherein R1 is methyl, R2 is isopropyl, R3 is methyl and X is hydrogen.
 9. The compound of claim 1, wherein R1 is methyl, R2 and R3 are isopropyl and X is hydrogen.
 10. The compound of claim 1, wherein R1 is ethyl, R2 is methyl, R3 is ethyl and X is hydrogen.
 11. The compound of claim 1, wherein R1 is ethyl, R2 is isopropyl, R3 is methyl and X is hydrogen.
 12. The compound of claim 1, wherein R1 is ethyl, R2 and R3 are isopropyl and X is hydrogen.
 13. The compound of claim 1, wherein R1 is n-propyl, R2 is methyl, R3 is isopropyl and X is hydrogen.
 14. The compound of claim 1, wherein R1 is isopropyl, R2 is methyl, R3 is ethyl and X is hydrogen.
 15. The compound of claim 1, wherein R1 is methyl, R2 is n-propyl, R3 is ethyl and X is chlorine.
 16. A compound of claim 1 in which R3 is isopropyl and X is hydrogen. 